Physico-chemical properties of C1q, such as sedimentation coefficients, intrinsic viscosities, solvent perturbation difference spectroscopy and hydrogen exchange, will be studied under a variety of conditions known to affect this macromolecule. Particular attention will be given to (1) thermal and acid instability, (2) effects of ionic strength, cations and chelating agents, (3) the role of collagen-like structures, and (4) numbers, locations and structural role of aromatic residues. These studies will form the basis for extensive hydrogen exchange experiments of C1q interacting with monomeric IgG, wherein exchange characteristics of each reacting component will be determined under a variety of conditions. From such studies attempts will be made to determine (1) role of conformational change, if any, upon binding for either component, (2) valence of C1q and binding affinity of these complexes, and (3) nature of the binding site on each macromolecule. The role of aromatic residues at the binding surfaces would also be determined from spectroscopy. C1q interactions with antigen reacted antibody will also be studied to assess conformational changes in C1q. Conditions would be varied in these studies to include: (1) C1q interacting with antigen-antibody complexes of various sizes and compositions, (2) C1q interacting with antigen complexed antibody reacting at one combining site, and (3) an identical system as item (2) but with antibody reacting through both combining sites. These experiments would be used to determine the role of aggregation of IgG in C1q binding relative to possible conformational changes in IgG as they might relate to binding. Model antigen-antibody reacting systems to be used in these studies will be the calcium dependent reactions which have been characterized in our laboratory.